Ratings of importance to the care process (A-C) and ratings of strength of evidence (I-III) are defined at the end of the "Major Recommendations" field.
Diagnosis
History
Obtaining a detailed history is important in evaluating patients with bacterial keratitis. Pertinent information includes the following:
- Ocular symptoms [A:III] (e.g., degree of pain, redness, discharge, blurred vision, photophobia, duration of symptoms, circumstances surrounding the onset of symptoms)
- Review of prior ocular history, [A:III] including risk factors such as contact lens wear, [A:II] swimming or using a hot tub while wearing contact lenses, herpes simplex virus keratitis, herpes zoster virus keratitis, previous bacterial keratitis, previous ocular surgery including refractive surgery, trauma, and dry eye
- Review of other medical problems [A:III]
- Current ocular medications and medications recently used [A:III]
- Medication allergies [A:III]
Examination
Visual Acuity
In many cases, patient discomfort, tearing, and inflammation will compromise visual acuity. It is useful, however, to document baseline visual acuity and to ascertain that it is consistent with the anterior segment examination. [A:III]
External Examination
An external examination should be performed with particular attention to the following:
- General appearance of the patient including skin conditions [B:III]
- Facial examination [B:III]
- Eyelids and lid closure [A:III]
- Conjunctiva [A:III]
- Nasolacrimal apparatus [B:III]
- Corneal sensation [A:III]
Slit-Lamp Biomicroscopy
Slit-lamp biomicroscopy should include evaluation of the following:
- Eyelid margins: [A:III] inflammation, ulceration, eyelash abnormalities including trichiasis, irregularities, lacrimal punctal anomalies
- Conjunctiva: [A:III] discharge, inflammation, morphologic alterations (e.g., follicles, papillae, cicatrization, keratinization, membrane, pseudomembrane, ulceration, prior surgery), ischemia, foreign bodies, filtering blebs
- Sclera: [A:III] inflammation (e.g., infectious versus autoimmune), ulceration, scarring/thinning, nodules, ischemia
- Cornea: [A:III] epithelium, including defects and punctate keratopathy, edema; stroma, including ulceration, thinning, perforation, and infiltrate (location [central, peripheral, perineural, surgical, or traumatic wound], density, size, shape [ring], number [satellite], depth, character of infiltrate margin [suppuration, necrosis, feathery, soft, crystalline], color), edema; endothelium; foreign bodies, including sutures; signs of corneal dystrophies (e.g., epithelial basement membrane dystrophies); previous corneal inflammation (thinning, scarring, or neovascularization); signs of previous corneal surgery (e.g., corneal transplantation, radial keratotomy, astigmatic keratotomy or limbal relaxing incision, LASIK, or other refractive surgery)
- Anterior chamber: [A:III] depth; inflammation, including cell and flare, hypopyon, fibrin, hyphema
- Anterior vitreous; [A:III] presence of inflammation
Clinical features suggestive of bacterial keratitis include dense suppurative stromal infiltrate (particularly those greater than 1 mm in size) with indistinct edges, edema, and white cell infiltration in surrounding stroma. An epithelial defect is typically present. An anterior chamber reaction is often seen.
Diagnostic Tests
Cultures and Smears
- Smears and cultures are indicated in cases with a corneal infiltrate that is large and extends to the middle to deep stroma, that is chronic in nature or unresponsive to broad spectrum antibiotic therapy, or that has clinical features suggestive of fungal, amoebic, or mycobacterial keratitis (Wilhelmus et al., 1994). [A:III]
- The hypopyon that occurs in eyes with bacterial keratitis is usually sterile, and aqueous or vitreous taps should not be performed unless there is a high suspicion of microbial endophthalmitis. [A:III]
- Prior to initiating antimicrobial therapy, cultures are indicated in sight-threatening or severe keratitis of suspected microbial origin. [A:III]
- Corneal scrapings for culture should be inoculated directly onto appropriate culture media in order to maximize culture yield (see Appendix 2 in the original guideline document) (Waxman et al., 1999). [A:III] If this is not feasible, specimens should be placed in transport media (Kaye et al., 2003). [A:III] In either case, cultures should be immediately incubated or taken promptly to the laboratory. [A:III] Cultures of contact lenses, lens case, and solution may be useful in situations where acanthamoeba is suspected or corneal cultures are negative. The material for smear is applied to clean class microscope slides in an even thin layer (see Appendix 3 in the original guideline document for specific diagnostic stains).
Corneal Biopsy
- Corneal biopsy may be indicated if there has been a lack of response to treatment or if cultures have been negative on more than one occasion and the clinical picture continues to strongly suggest an infectious process. It may also be indicated if the infiltrate is located in the mid or deep stroma with overlying uninvolved tissue.
- The biopsy specimen should be delivered to the laboratory in a timely fashion. [A:III]
Treatment
Initial
- Topical antibiotic eye drops are capable of achieving high tissue levels and are the preferred method of treatment in most cases. [A:III] Ocular ointments may be useful at bedtime in less severe cases and also may be useful for adjunctive therapy.
- Subconjunctival antibiotics may be helpful where there is imminent scleral spread or perforation or in cases where adherence to the treatment regimen is questionable. Systemic therapy may be useful in cases of scleral or intraocular extension of infection or systemic infection such as gonorrhea. Collagen shields or soft contact lenses soaked in antibiotics are sometimes used and may enhance drug delivery. They may also be useful in cases where there is an anticipated delay in initiating appropriate therapy, but these modalities have not been fully evaluated in terms of the potential risk for inducing drug toxicity.
- Topical broad-spectrum antibiotics are used initially in the empiric treatment of bacterial keratitis [A:III] (see Table 2 in the original guideline document). For severe keratitis (e.g., deep stromal involvement or a defect larger than 2 mm with extensive suppuration), a loading dose every 5 to 15 minutes for the first hour, followed by applications every 15 minutes to 1 hour around the clock, is recommended. [A:III] For less severe keratitis, a regimen with less frequent dosing is appropriate. Cycloplegic agents may be used to decrease synechia formation and to decrease pain in more severe cases of bacterial keratitis and are indicated when significant anterior chamber inflammation is present.
- Systemic antibiotics are rarely needed, but may be considered in severe cases where the infectious process has extended to adjacent tissues (e.g., the sclera) or when there is impending or frank perforation of the cornea. Systemic therapy is necessary in cases of gonococcal keratitis. [A:III]
- Frequency of re-evaluation of the patient with bacterial keratitis depends on the extent of disease, but severe cases (e.g., deep stromal involvement or larger than 2 mm with extensive suppuration) initially should be followed at least daily until clinical improvement or stabilization is documented. [A:III]
Modification of Therapy
- In general, the initial therapeutic regimen should be modified when the eye shows a lack of improvement or stabilization within 48 hours. [A:III] Keratitis due to Pseudomonas and other gram-negative organisms may exhibit increased inflammation during the first 24 to 48 hours despite appropriate therapy. Several clinical features suggest a positive response to antibiotic therapy:
- Reduction in pain
- Reduced amount of discharge
- Lessened eyelid edema or conjunctival injection
- Consolidation and sharper demarcation of the perimeter of the stromal infiltrate
- Decreased density of the stromal infiltrate in the absence of progressive stromal loss
- Reduced stromal edema and endothelial inflammatory plaque
- Reduced anterior chamber cell, fibrin, or hypopyon
- Initial re-epithelialization
- Cessation of progressive corneal thinning
- Modification of therapy may mean a change in the type, concentration, or frequency of antibiotic treatment. Adjunctive therapy such as a temporary or permanent tarsorrhaphy may also be considered.
- Topical therapy is tapered according to clinical response, taking into account the severity of the initial clinical picture and the virulence of the pathogen. Specific tapering recommendations are difficult to make, due to wide variability in the severity of the infectious process in individual cases. Factors that may mandate more prolonged therapy include the presence of virulent or indolent organisms or presence of immunocompromise.
Indications for Reculture
Lack of a favorable clinical response, particularly in the setting of negative culture results, suggest the need for reculture and/or biopsy.
Corticosteroid Therapy
- Topical corticosteroid therapy may have a beneficial role in treating some cases of infectious keratitis.
- Patients being treated with ocular topical corticosteroids at the time of presentation of suspected bacterial keratitis should have their corticosteroid regimen reduced or eliminated until the infection has been controlled. [A:III]
- The objective in topical corticosteroid therapy is to use the minimum amount of corticosteroid required to achieve control of inflammation. Successful treatment requires optimal timing, careful dose regulation, use of adequate concomitant antibacterial medication, and close follow-up. Patient compliance is essential, and the intraocular pressure must be monitored frequently. The patient should be examined within 1 to 2 days after initiation of topical corticosteroid therapy. [A:III]
Therapy for Complicated Cases
- Additional treatment is necessary in cases where the integrity of the eye is compromised, such as an extremely thin corneal surface, or impending or frank perforation, or where there is progressive or unresponsive disease or endophthalmitis. Application of tissue adhesive, lamellar keratoplasty, and penetrating keratoplasty are among the treatment options.
Provider and Setting
- The diagnosis and management of patients with bacterial keratitis require the clinical training and experience of an ophthalmologist because the disease has the potential to cause visual loss or blindness and because the ophthalmologist is familiar with medical conditions associated with bacterial keratitis. [A:III] Severe cases, or those that fail to respond to treatment, may be best managed by an ophthalmologist who has extensive expertise with bacterial keratitis.
- The majority of patients with bacterial keratitis can be treated on an outpatient basis. Hospitalization may be necessary if the keratitis is severe or vision threatening, if compliance is impractical, or if pain is severe.
Counseling/Referral
- Patients and care providers should be educated about the destructive nature of bacterial keratitis and the need for strict adherence to the therapeutic regimen. [A:III]
- The possibility of permanent visual loss and need for future visual rehabilitation should be discussed. [A:III]
- Patients who wear contact lenses should be educated about the increased risk of infection associated with contact lens wear, overnight wear, and the importance of adherence to techniques that promote contact lens hygiene (Larkin, Kilvington, & Easty, 1990; Stern, 1998). [A:III]
- Patients with significant visual impairment or blindness should be referred for vision rehabilitation if they are not candidates for surgical visual rehabilitation (American Academy of Ophthalmology, 2001). [A:III]
Definitions:
Ratings of Importance to Care Process:
Level A, most important
Level B, moderately important
Level C, relevant, but not critical
Ratings of Strength of Evidence:
- Level I includes evidence obtained from at least one properly conducted, well-designed randomized, controlled trial. It could include meta-analyses of randomized controlled trials.
- Level II includes evidence obtained from the following:
- Well-designed controlled trials without randomization
- Well-designed cohort or case-control analytic studies, preferably from more than one center
- Multiple-time series with or without the intervention
- Level III includes evidence obtained from one of the following:
- Descriptive studies
- Case reports
- Reports of expert committees/organization
- Expert opinion (e.g., Preferred Practice Pattern panel consensus)
